Boosting Cancer Immunotherapy with Anti-CD137 Antibody Therapy

Abstract

In the past 5 years, immunomodulatory antibodies have revolutionized cancer immunotherapy. CD137, a member of the tumor necrosis factor receptor superfamily, represents a promising target for enhancing antitumor immune responses. CD137 helps regulate the activation of many immune cells, including CD4(+) T cells, CD8(+) T cells, dendritic cells, and natural killer cells. Recent studies indicate that the antitumor efficacy of therapeutic tumor-targeting antibodies can be augmented by the addition of agonistic antibodies targeting CD137. As ligation of CD137 provides a costimulatory signal in multiple immune cell subsets, combination therapy of CD137 antibody with therapeutic antibodies and/or vaccination has the potential to improve cancer treatment. Recently, clinical trials of combination therapies with agonistic anti-CD137 mAbs have been launched. In this review, we discuss the recent advances and clinical promise of agonistic anti-CD137 monoclonal antibody therapy.

Figure 1

Immunomodulatory mechanisms of CD137. CD137 is expressed in several immune cells. Agonistic anti-CD137 mAb increases T-cell proliferation, differentiation to memory cells, and resistance to apoptosis in CD8⁺ T cells. In addition, anti-CD137 mAb can depress Treg function. In DCs, anti-CD137 mAb with vaccination enhances tumor antigen presentation and costimulation to increase the functions of antitumor CTLs. One of the primary mechanisms of antitumor activity of mAbs is antibody-dependent cell-mediated cytotoxicity (ADCC). On NK cells, stimulation of CD137 enhances ADCC. Agonistic anti-CD137 mAb stimulates CD8⁺ T cells, Tregs, DCs, and NK cells to induce potent antitumor immune response. MHC, major histocompatibility complex; TCR, T-cell receptor.